P-1225. Aztreonam/Avibactam vs. Aztreonam Plus Ceftazidime/Avibactam for Multidrug-Resistant Stenotrophomonas maltophilia

Abstract Background Stenotrophomonas maltophilia is an opportunistic pathogen affecting vulnerable patients, including those with hematologic malignancies and chronic lung disease. Due to limited treatment options, outcomes remain poor. The IDSA recommends aztreonam plus ceftazidime/avibactam (ATM+CZA), while the recently FDA-approved aztreonam/avibactam (ATM/AVI) shows high in vitro activity. However, comparative efficacy data are lacking. Methods We evaluated ATM+CZA and ATM/AVI against 24 clinical S. maltophilia isolates—15 from hematologic malignancy patients at MD Anderson (MD isolates) and 9 from chronic lung disease patients at UK Healthcare in Lexington (UK isolates). MICs were determined in triplicate by broth microdilution per CLSI guidelines; ATM/AVI MICs were verified using gradient diffusion strips (AbbVie). Time-kill assays were performed at clinically relevant Cmax concentrations of ATM, CAZ, and AVI. Bactericidal activity was defined as a ≥3-log₁₀ CFU/mL reduction from baseline. All isolates underwent whole-genome sequencing to characterize resistance mechanisms and provide genomic context for phenotypic findings (Table 1). Results Among 24 S. maltophilia isolates, MIC₅₀/₉₀ values were 2/8 µg/mL for ATM+CZA and 4/16 µg/mL for ATM/AVI (Table 2). Time-kill analysis demonstrated bactericidal activity with both regimens across multiple isolates, though ATM/AVI showed more consistent killing overall (Table 3). Notable discordances between MIC and killing activity were observed. Isolates MD17061 and MD17639 had identical MICs (4 µg/mL) for both regimens, yet ATM/AVI produced significantly greater bacterial killing (P=0.014 and P< 0.001, respectively) (Figure 1A,B). Conversely, MD17229 and MD16852 exhibited large MIC differences (ATM+CZA< 0.25 µg/mL vs ATM/AVI 8 µg/mL) but similar bactericidal activity (Figure 1C,D). Conclusion ATM/AVI demonstrated more consistent bactericidal activity than ATM+CZA, including in isolates with similar or less favorable MICs. Discordance between MIC and killing highlights the need for functional testing to guide treatment of multidrug-resistant S. maltophilia. Disclosures All Authors: No reported disclosures